Enhanced T Cell Attack of Brain Micro-Metastases
Abstract
Our goal is to increase the efficacy of T cell attack against breast cancer that has metastasized to the brain. This is a major clinical problem, and T cell therapy is well-suited to attack of tumor that may be difficult to image or access conventionally. The first task was to develop a suitable model: (1) We adapted methods for introducing tumor into the carotid artery, to favor delivery to the brain. (2) We modified the rat mammary carcinoma cell line, 13762 MAT Bill, so that it expresses the IacZ reporter gene product, E. coli b-galacotsidase (b-gal)(MATB/IacZ). The b-gal permits unambiguous identification of even single tumor cells and serves as a defined tumor antigen. (3) We showed that after intra-carotid injection of MATB/IacZ, metastases do appear in the brain. The sites of metastatic tumor and time-to-illness are dose-dependent. The time-to-illness is sufficient for our goals. (4) Our therapy involves introducing activated, tumor-specific T cells into the blood and injecting immuno-activating cytokine (IFN-g) into the brain. We developed fluorescence-labeled T cell lines that allow unambiguous identification of the responding T cells, and did other preparatory work. Now we are ready to test our proposed therapy. The model itself is of general interest.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA400084
Entities
People
- Lois Lampson
Organizations
- Brigham and Women's Hospital